VACCINE VISIONARIES

Discovery of the BCG vaccine

Léon Charles Albert Calmette (1863-1933) was a French physician, bacteriologist and immunologist. In 1890, after having met Louis Pasteur and Emile Roux, he became an associate at the Pasteur Institute. Later, he founded and directed a branch in Saigon, French Indochina, where he dedicated himself to the nascent field of toxicology. When, in 1894, he came back to France, he developed the first antivenom for snake bites, which was to be named Calmette's serum, using immune sera from vaccinated horses.

Albert Calmette

Camille Guerin

          
In 1895, Calmette was entrusted with the directorship of the Pasteur Institute's branch at Lille. A few years later, French veterinarian Jean-Marie Camille Guerin (1872-1961) joined the Institute. He started as a technician in charge of preparing Calmette's serum, but was soon promoted to Head of Laboratory.

Before long, Calmette and Guerin started working on developing a vaccine for tuberculosis, which was a major killer disease at the time. German biologist Robert Koch had discovered that Mycobacterium tuberculosis was its pathogenic agent and, by 1905, Guerin had established that the bovine tuberculosis bacillum, the Mycobacterium bovis, could immunize animals without causing the disease. Calmette then investigated how immunity would develop in response to attenuated bovine bacilli injected in animals, using Pasteur's approach. From then onwards, Guerin, who in 1919 was promoted to head of services, and Calmette developed ways of attenuating the pathogenic activity of Mycobacterium, striving to produce less and less virulent strains of the bacillus, by transferring them to successive cultures.

Finally, in 1921, Bacillus Calmette-Guerin (BCG), the vaccine for immunization against tuberculosis, was first used in humans.

In the meantime, Calmette had founded the first anti-tuberculosis dispensary at Lille, and the "Ligue du Nord contre la Tuberculose" (Northern Anti-tuberculosis League), which exists until today. Guerin, on the other hand, became the director of the Tuberculosis Service at the Pasteur Institute in Paris.

In 1928, BCG was adopted by the Health Committee of the League of Nations (predecessor of the WHO). Public acceptance of the vaccine, however, was slow, and the vaccination program suffered a major setback in 1930, when some batches of the vaccine were contaminated by a virulent strain in Lubeck, Germany, causing the death of 72 infants.

The Lubeck disaster The Lubeck disaster will remain a landmark in the history of immunization. In the summer of 1930, in Lubeck, Germany, 240 infants were vaccinated with BCG; 72 of the vaccinated infants developed tuberculosis and died. It was then discovered that the BCG administered had been contaminated with a virulent strain that was being stored in the same incubator. There was an uproar against BCG all over the world, and legal action was taken against the manufacturers. An inquiry exonerated the BCG manufacturers, however, as it was found that the blunder had occurred in the Lubeck laboratory, whose in charge was sentenced to 2 years' imprisonment. Nevertheless, the disaster had done much to harm public acceptance of the vaccine, and mass vaccination of children was only reinstated after 1932, when new and safer production techniques were implemented.

Due to opposition, BCG did not become widely used until after World War II, when relief organizations (International Tuberculosis Campaign or Joint Enterprises) vaccinated over 8 million babies in Eastern Europe, and prevented the predicted increase of TB after a major war.

Guerin became vice-president of the "Comité National de Défense contre la Tuberculose" (National Defense Committee against Tuberculosis) in 1939, and in 1948, he was chairman of the First International Congress on BCG. In 1955, the French Academy of Sciences awarded him the Scientific Grand Prix.

BCG is very efficacious against tuberculous meningitis in the paediatric age group, but its efficacy against pulmonary tuberculosis appears to be variable depending on geography. According to research, the BCG vaccine is at best 80% effective in preventing tuberculosis for a duration of 15 years. As of 2006, only a few countries, including the US and the Netherlands, do not use BCG for routine vaccination.